The theme of this Center is "Biochemical and Molecular Mechanisms Underlying Human Variability in Response to Environmental Exposures". The interactions between genetics and environment are complex, and defy explanation through traditional disciplinary pathways of investigation. Recent developments in molecular biology provide exciting new tools that can be used directly in human populations to unravel the molecular basis for differences in susceptibility to environmental hazards. The purpose of this proposed NIEHS Center is to provide an administrative infrastructure and technical support to foster the multidisciplinary collaborations necessary to extend basic mechanistic studies on environmental health problems to direct application in human populations. This Center will for the first time provide an organizational incentive to bring together the broad array of well established scientists at the University of Washington who work on diseases with an environmental etiology. This center will consist of 6 research cores: 1) Xenobiotic biotransformation and disposition, 2) Mechanisms of free radical tissue injury, 3) Reproductive and developmental toxicology, 4) Neurotoxicology, 5) Respiratory toxicology and 6) Environmental epidemiology. Each of these Cores consist of 7 - 10 senior investigators and 2 - 4 associate investigators representing several different Departments and programs throughout the University. The funded research of these core faculty will be enhanced by 5 Services cores which will provide Center investigators access to: 1) human populations and tissues, 2) state-of-the-art molecular biology tools and resources to assist in the conduct of large scale molecular biomarker work, 3) analytical cytology techniques such a flow cytometry and fluorescence activated quantitative cytometry, 4) a mobile laboratory which can be used to conduct field investigations for a variety of purposes (e.g., computerized neurobehavioral function, pulmonary function, biological sample collection, genetic family studies), and 5) support for development and maintenance of transgenic animals of value in toxicological research. A Community Outreach and Education Core provides a mechanism to disseminate important research findings of Center investigators to the general community, as well as a coordinating function to extend and enhance existing community education programs to include more emphasis on issues related to environmental health sciences.